Acute serotonin 2A receptor blocking alters the processing of fearful faces in the orbitofrontal cortex and amygdala

TY - JOUR

T1 - Acute serotonin 2A receptor blocking alters the processing of fearful faces in the orbitofrontal cortex and amygdala

AU - Hornboll, Bettina

AU - Macoveanu, Julian

AU - Rowe, James

AU - Elliott, Rebecca

AU - Paulson, Olaf B

AU - Siebner, Hartwig R

AU - Knudsen, Gitte M

PY - 2013/10

Y1 - 2013/10

N2 - Background: The serotonin 2A (5-HT2A) receptor has been implicated in neural-processing of emotionally salient information. To elucidate its role in processing of fear and anger, healthy individuals were studied with functional magnetic resonance imaging (fMRI) after 5-HT2A receptor blockade, while judging the gender of neutral, fearful and angry faces. Methods: 5-HT2A receptors were blocked with ketanserin to a variable degree across subjects by adjusting the time between ketanserin-infusion and onset of the fMRI protocol. Neocortical 5-HT2A receptor binding in terms of the binding potential (BPp) was assessed prior to fMRI with 18F-Altanserin positron emission tomography (PET) and subsequently integrated in the fMRI data analysis. Also functional connectivity analysis was employed to evaluate the effect of ketanserin blocking on connectivity. Results: Compared to a control session, 5-HT2A receptor blockade reduced the neural response to fearful faces in the medial orbitofrontal cortex (OFC), independently of 5-HT2A receptor occupancy or neocortical 5-HT2A receptor BPp. The medial OFC also showed increased functional coupling with the left amygdala during processing of fearful faces depending on the amount of blocked 5-HT2A receptors. Conclusions: 5-HT2A receptor mediated signaling increases the sensitivity of the OFC to fearful facial expressions and regulates the strength of a negative feedback signal from the OFC to amygdala during processing of fearful faces.

AB - Background: The serotonin 2A (5-HT2A) receptor has been implicated in neural-processing of emotionally salient information. To elucidate its role in processing of fear and anger, healthy individuals were studied with functional magnetic resonance imaging (fMRI) after 5-HT2A receptor blockade, while judging the gender of neutral, fearful and angry faces. Methods: 5-HT2A receptors were blocked with ketanserin to a variable degree across subjects by adjusting the time between ketanserin-infusion and onset of the fMRI protocol. Neocortical 5-HT2A receptor binding in terms of the binding potential (BPp) was assessed prior to fMRI with 18F-Altanserin positron emission tomography (PET) and subsequently integrated in the fMRI data analysis. Also functional connectivity analysis was employed to evaluate the effect of ketanserin blocking on connectivity. Results: Compared to a control session, 5-HT2A receptor blockade reduced the neural response to fearful faces in the medial orbitofrontal cortex (OFC), independently of 5-HT2A receptor occupancy or neocortical 5-HT2A receptor BPp. The medial OFC also showed increased functional coupling with the left amygdala during processing of fearful faces depending on the amount of blocked 5-HT2A receptors. Conclusions: 5-HT2A receptor mediated signaling increases the sensitivity of the OFC to fearful facial expressions and regulates the strength of a negative feedback signal from the OFC to amygdala during processing of fearful faces.

U2 - 10.1177/0269881113494106

DO - 10.1177/0269881113494106

M3 - Journal article

C2 - 23824248

SN - 0269-8811

VL - 27

SP - 903

EP - 914

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

IS - 10

ER -